1. Field of the Invention
The present invention describes a method for preparing dicarbonyl compounds of the general formula: ##STR4##
In one embodiment, "R" is CH.sub.3 and "Z" is COCH.sub.3, and a product known as 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione is formed, shown in the following formula: ##STR5##
In another embodiment, "R" is CH.sub.3 and "Z" is CO.sub.2 CH.sub.2 CH.sub.3, and the product, ethyl 2-(3-methyl-2-buten-1-yl)-3-oxobutanoate, is formed, shown in the following formula: ##STR6##
2. Description of Related Art
(a) Prior Art Processes for Preparation of Dicarbonyl Compounds (7)
The invention relates to a new method for conversion of isoprene (or other 2-alkyl-1,3-butadienes) to dicarbonyl compounds of the general structure (7). For previous syntheses of 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione (7a), see the following:
(a) European Patent Appl. EP 44,771 (Jan. 27, 1982) [Chem. Abstracts 1982, 96, 199115b]. PA1 (b) J. A. Miller, et al., J. Chem. Soc. Perkin I 1972, 692. PA1 (c) H. Pommer, et al., Justus Liebigs Ann. Chem. 1969, 729, 52. PA1 (d) German patent 1,914,376 (Oct. 1, 1970) [Chem. Abstracts 1970, 73, 120090h]. PA1 (e) U.S. Pat. No. 3,998,872 (Dec. 21, 1976) [Chem. Abstracts 1977, 86, 89179m]. PA1 (f) J. Marquet and M. Moreno-Manas, Synthesis 1979, 348. PA1 (g) Chem. Abstracts 1980, 93, 26559j. PA1 (h) M. Moreno-Manas and A. Trius, Tetrahedron 1981, 37, 3009. PA1 (i) J. Marquet, et al., Tetrahedron Lett. 1988, 29, 1465. PA1 (a) H. Pommer, et al., Justus Liebigs Ann. Chem. 1969, 729, 52. PA1 (b) European Patent Appl. EP 44,771 (Jan. 27, 1982) [Chem. Abstracts 1982, 96, 199115b). PA1 (c) French patent 2,567,511 (Jan. 17, 1986) [Chem. Abstracts 1986, 105, 171857a]. PA1 (d) A. A. Petrov, et al., Zh. Obshch. Khim. 1963, 33, 427 [Chem. Abstracts 1963, 59 431c]. PA1 (e) U.S. Pat. No. 3,420,827 (Jan. 7, 1969) [Chem. Abstracts 1969, 70 67626x]. PA1 (f) S. Julia and G. Linstrumelle, Bull. Soc. Chim. France 1966, 3490. PA1 (g) Czech. patent 112,243 (Oct. 15, 1964) [Chem. Abstracts 1965, 62, 13049e]. PA1 (i) an inorganic acid possessing a K.sub.a (relative to water) that is greater than 10.sup.-3. Phosphoric acid (85-100%) and polyphosphoric acid are preferred catalysts. Aqueous sulfuric acid (H.sub.2 SO.sub.4) can also be used to catalyze this process, although it is not a preferred catalyst. PA1 (ii) an organic acid possessing a K.sub.a (relative to water) that is greater than 10.sup.-1. Sulfonic acids (RSO.sub.3 H) are useful catalysts for this process--e.g., p-toluenesulfonic acid monohydrate (Example VI). PA1 (iii) The acid catalyst does not have to be soluble in the reaction mixture. For example, strongly acidic resins can be used to catalyze the process (Example VII). PA1 (iv) Hydrochloric acid (HCl), although it is a strong acid, cannot be used to catalyze this process (Example V). Although the "prenyl cation" is generated when HCl protonates isoprene, the chloride anion traps the intermediate--thereby generating (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 Cl, not the desired product (7). PA1 (a) No costly raw materials are utilized. PA1 (b) The process avoids the use of organic halides. PA1 (c) Mixtures of isomeric products are not a serious problem in the conversion of isoprene to dicarbonyl compound (7). The latter product is easy to purify since (7a) is soluble in dilute aqueous NaOH (in contrast to the by-products). PA1 (d) The disclosed process generates a product (7), and subsequently (9) that possesses the correct structure for the preparation of valuable specialty chemicals such as linalool, citral, pseudoionone, and lycopene. BASF's route to "methyl-heptenone" generates an isomeric compound (14) that can only be used to prepare .alpha.- or .beta.-ionone.
All of the above routes involved multi-step processes and/or costly reagents; and all involved the formation of substantial amounts of undesirable isomeric by-products. Furthermore, most of these previous syntheses of 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione (7a) involved the preparation of expensive intermediates [e.g., (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 Cl or (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 OH] from isoprene prior to the chemical step used to generate diketone (7a). For two notable exceptions, see references (a) and (e) cited above. However, both of the latter processes afforded unattractive mixtures of products and required costly metallic catalysts.
For previous syntheses of ethyl 2-(3-methyl-2-buten-1-yl)-3-oxobutanoate (7b), see:
(b) Utility of Dicarbonyl Compounds (7)
The dicarbonyl compounds (7) may be used in the synthesis of pseudoionone (2) (systematically named as 6,10-dimethyl-3,5,9-undecatrien-2-one), according to the following reaction sequence: ##STR7##
Pseudoionone (2) is a costly specialty chemical that is used in the manufacture of .alpha.-ionone (3), used in perfumery, and .beta.-ionone (4), used in perfumery as well as in the manufacture of vitamin A, the anti-acne drugs tretinoin (sold by Ortho Pharmaceutical Corp. under the registered trademark Retin-A) and isotretinoin (sold by Hoffmnan-LaRoche Inc. under the registered trademark Accutane), and several widely used carotenoids, including beta-carotene and canthaxanthin. Pseudoionone can also be used in the manufacture of vitamin E [see: U.S. Pat. No. 5,349,071 (Sep. 20, 1994)] since it is easily converted to isophytol.
One of the earliest routes to pseudoionone involved a crossed-aldol condensation between citral (1) and acetone as shown below: ##STR8## References: Organic Syntheses, Collective Volume 3, page 747; H. Hibbert and L. T. Cannon, J. Am. Chem. Soc., 46, 119-130 (1924). The major disadvantage to this route is that it involves use of the costly specialty chemical citral (1), systematically named as 3,7-dimethylocta-2,6-dienal, which is manufactured in a multi-step process generally involving at least five transformations. Once pseudoionone (2) has been obtained, however, it can be converted in high yield and in one step to either .alpha.-ionone (3) or .beta.-ionone (4) with little additional cost. ##STR9##
A very attractive alternative route to a structural analogue (18) of pseudoionone that avoids the use of citral has been developed by BASF and is outlined below: ##STR10##
Although BASF's C-13 polyenone (18) can be converted to .beta.-ionone, polyenone (18) does not possess the correct structure one would need to prepare carotenoids such as lycopene, the red coloring matter of tomatoes. Lycopene has recently been shown to have many useful properties, especially in giving protection against prostate cancer, heart disease, and degenerative eye diseases. Furthermore, the C-8 unsaturated ketone (14) in BASF's route does not possess the proper structure for manufacture of the specialty chemicals linalool (widely used in perfumery) and citral (used extensively in the flavor and fragrance industries). Both of the latter specialty chemicals can be manufactured using known industrial processes starting with the unsaturated ketone (9) obtained in the route of the presently disclosed invention (see section 2(c), below). Likewise, carotenoids such as lycopene are readily prepared from our unsaturated ketone intermediate. An additional advantage of the disclosed process for obtaining C-8 unsaturated ketone (9) from isoprene is that fact that the overall yield is higher and the process is easier to conduct (e.g., atmospheric pressure, room temperature) than the one developed by BASF.
(c) Other Uses of Unsaturated Ketone (9), Produced as an Intermediate in the Synthesis of Pseudoionone
Unsaturated ketone (9), shown as a product in step (b) of Scheme I above, may also be used to produce linalool (19) (3,7-dimethyl-1,6-octadien-3-ol, widely used in perfumery) and citral (1) (used extensively in the flavor and fragrance industries), according to the following reaction sequence: ##STR11##